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Human neural stem cells alleviate Alzheimer-like pathology in a mouse model

Authors
 Il-Shin Lee  ;  Kwangsoo Jung  ;  Il-Sun Kim  ;  Haejin Lee  ;  Miri Kim  ;  Seokhwan Yun  ;  Kyujin Hwang  ;  Jeong Eun Shin  ;  Kook In Park 
Citation
 Molecular Neurodegeneration, Vol.10 : 38, 2015 
Journal Title
 Molecular Neurodegeneration 
ISSN
 1750-1326 
Issue Date
2015
Abstract
BACKGROUND: Alzheimer's disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. RESULTS: Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. CONCLUSIONS: These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a safe and versatile approach for treating AD patients.
Files in This Item:
T201503945.pdf Download
DOI
10.1186/s13024-015-0035-6
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Mi Ri(김미리)
Kim, Il-Sun(김일선) ORCID logo https://orcid.org/0000-0003-4033-4323
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Shin, Jeong Eun(신정은) ORCID logo https://orcid.org/0000-0002-4376-8541
Yun, Seok Hwan(윤석환)
Jung, Kwang Soo(정광수) ORCID logo https://orcid.org/0000-0001-7365-7247
Hwang, Kyujin(황규진) ORCID logo https://orcid.org/0000-0001-5193-5154
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141490
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